In vivo investigation of tolerance and antitumor activity of cisplatin-loaded PLGA-mPEG nanoparticles.
The tolerance of BALB/c mice to different doses of blank and cisplatin-loaded PLGA-mPEG nanoparticles and the in vivo anticancer activity of these nanoparticles on SCID mice xenografted with colorectal adenocarcinoma HT 29 cells were investigated. Nanoparticles with an average size of 150-160 nm and approximately 2% w/w cisplatin content were prepared by a modified emulsification and solvent evaporation method. Normal BALB/c mice tolerated three weekly intravenous injections of a relatively high dose of blank PLGA-mPEG nanoparticles (500 mg/kg, equivalent to about 10mg nanoparticles/mouse) and three weekly intravenous injections of a high dose of nanoparticle-entrapped cisplatin (10 mg/kg). Also, histopathology examination indicated that there were no differences in the kidneys or spleens from animals treated with cisplatin-loaded nanoparticles or blank nanoparticles compared to the untreated control group. A moderate granulation of protoplasm of hepatic cells was observed in the livers from mice treated with cisplatin-loaded nanoparticles and blank nanoparticles, however, both the hepatic lobe and the portal hepatis maintained their normal architecture. The cisplatin-loaded PLGA-mPEG nanoparticles appeared to be effective at delaying tumor growth in HT 29 tumor-bearing SCID mice. The group of mice treated with cisplatin-loaded nanoparticles exhibited higher survival rate compared to the free cisplatin group. The results justify further evaluation of the in vivo antitumor efficacy of the PLGA-mPEG/cisplatin nanoparticles.
Mattheolabakis
George
G
Department of Pharmacy, University of Patras, Rio, Greece.
Taoufik
Era
E
Haralambous
Sylva
S
Roberts
Michael L
ML
Avgoustakis
Konstantinos
K
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D053758:Nanoparticles; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D015996:Survival Rate; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004337:Drug Carriers; D011091:Polyesters; C558447:methoxypolyethyleneglycol-poly(lactic-co-glycolic acid); D011098:Polyglactin 910; D011092:Polyethylene Glycols; D002945:Cisplatin